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L. Wang
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-022 - Protein Tyrosine Phosphatase Interacting Protein 51 Might Improve EGFR-TKI Sensitivity in Non-Small-Cell Lung Cancer (ID 8043)
09:30 - 09:30 | Author(s): L. Wang
- Abstract
Background:
Epidermal growth factor receptor (EGFR) -mutant tumors define a subset of Non-small-cell lung cancer (NSCLC), tumors that harbor EGFR mutation are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib. However, acquired resistance develops in most NSCLC patients with EGFR mutations after 10-14 months of treatment. In this study we aimed to testify the tumor suppressing function of Protein tyrosine phosphatase interacting protein 51 (PTPIP51), an apoptosis related protein and its effect in improving EGFR-TKI sensitivity.
Method:
Tumor tissues and matched adjacent normal tissues of 154 patients undergoing surgery in the department of Thoracic Surgery II of Beijing Cancer Hospital during 2006–2011 were tested. Patient-derived xenograft mice (PDX model) carrying primary tumor was prepared and Gefitinib/adenovirus-PTPIP51 were used for treatment in vivo and vitro.
Result:
PTPIP51 was down-regulated in NSCLC on both RNA and protein level, and high PTPIP51 expression was revealed as a favorable predictor for better outcome of NSCLC patients(Figure A,B), and elevated PTPIP51 expression exhibited a higher objective regression rate(ORR) to EGFR-TKI therapy of patients with EGFR mutation. Sensitivity to EGFR-TKI of PC9 and A549 cell lines were both enhanced after transfection of PTPIP51. After treatment with adenovirus-PTPIP51+placebo, Gefitinib+placebo, and PTPIP51 plus Gefitinib, it suggested that PTPIP51 could significantly improve EGFR-TKI efficacy in PDX model with wild-type NSCLC tumors (Figure C,D), suggesting a potential correlation between PTPIP51 and EGFR signal pathways. Over-expression of PTPIP51 in NSCLC cell lines significantly inhibited the downstream signaling of EGFR, including PI3K/Akt, Ras/Raf/Erk and Jak/Stat3 pathways, and Gefitinib co-effected with PTPIP51 could induce apoptosis of NSCLC cell lines PC9 and A549. Meanwhile, PTPIP51 interacted with PTEN could induce ubiquitylation then degradation of EGFR via lysosome. Figure 1
Conclusion:
Our findings first highlighted PTPIP51 as a novel tumor suppressor gene in NSCLCs, and it might play a potential role in outcome prediction and improvement of EGFR-TKI sensitivity.
